The platelet as a therapeutic target for treating vascular diseases and the role of eicosanoid and synthetic PPARγ ligands

Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, New York, United States
Prostaglandins & other lipid mediators (Impact Factor: 2.38). 02/2007; 82(1-4):68-76. DOI: 10.1016/j.prostaglandins.2006.05.018
Source: PubMed


The platelet was traditionally thought only to serve as the instigator of thrombus formation, but now is emerging as a pivotal player in cardiovascular disease and diabetes by inciting and maintaining inflammation. Upon activation, platelets synthesize eicosanoids such as thromboxane A2 (TXA2) and PGE2 and release pro-inflammatory mediators including CD40 ligand (CD40L). These mediators activate not only platelets, but also stimulate vascular endothelial cells and leukocytes. These autocrine and paracrine activation processes make platelets an important target for attenuating inflammation. The growing interest and recent discoveries in platelet biology has lead to the search for therapeutic platelet targets. Recently, platelets, although anucleate, were discovered to possess the transcription factor PPARgamma. Treatment with eicosanoid and synthetic PPARgamma ligands blunts platelet release of the bioactive mediators, soluble (s) CD40L and TXA2, in thrombin-activated platelets. PPARgamma ligand treatment may prove useful for dampening unwanted platelet activation and chronic inflammatory diseases such as cardiovascular disease.

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    • "PPARs play important roles in the regulation of metabolic pathways, including lipid biosynthesis and glucose metabolism [10,11]. This and implicated roles in cell differentiation, proliferation and inflammation have led to the hypothesis that the actions of PPARs may be associated with the prevention of cardiovascular complications [10–12]. Although platelets lack a nucleus, we and others have reported that they express a number of transcription factors including the steroid/nuclear receptors such as PPARγ, PPARβ/δ, the glucocorticoid receptor (GR), oestrogen receptor (ER), retinoic X receptor (RXR) and NF-κB [13–19]. "
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